Antipsychotics extrapyramidal side effects

Antipsychotics are not indicated for the treatment of withdrawal, except when hallucinations or severe agitation are present (Naranjo and Sellers 1986), in which case they should be added to a benzodiazepine. In addition to their potential to produce extrapyramidal side effects, antipsychotics lower the threshold for seizures, which is particularly problematic during alcohol withdrawal. 

It has been suggested that high affinity for certain 5-HT receptors is a possible method for reducing extrapyramidal side effects observed with antipsychotics. LiabiUty for extrapyramidal side effects has been hypothesi2ed to be related to the ratio of the affinity between dopamine receptor... 

Chlorpromazine had been shown to produce a tranquil state in animals and since it had a similar effect in humans it became known as a major tranquiliser but the term is rarely used today. Sometimes the drugs used to treat schizophrenia are called anti-psychotics but more commonly neuroleptics. Leptic means to activate (take hold of) and in animals these compounds produce a state of maintained motor tone known as catalepsy. This is an extrapyramidal effect and in schizophrenics the neuroleptics can cause a number of extrapyramidal side-effects (EPSs) including Parkinsonism. The new term neuroleptic is unsatisfactory as a description of clinically useful drugs. It really describes a condition (catalepsy) seen in animals and is more indicative of a compound s ability to produce EPSs than to treat schizophrenia. Antipsychotic is more descriptive but could imply a more general efficacy in psychoses than is the case. It would seem more appropriate to call a drug that is used to treat schizophrenia an antischizophrenic just as we use the terms antidepressant or antiepileptic irrespective of how the drug works. Despite such personal reservations, the term neuroleptic will be used in this text. 

Extrapyramidal side effects These are caused by antipsychotic drugs. They are characterised by motor and postural disturbances, of which the most serious is late-onset tardive dyskinesia. 

Extrapyramidal side-effects generally appear with blockade of dopamine D2 receptors in excess of 80%, whereas clinical efficacy in treating psychosis is associated with 60-70% D2 receptor blockade [12]. Recently, a partial agonist for the D2 receptor known as aripiprazole has been developed, which results in approximately 70% antagonism/30% agonism at the D2 receptor. It is an effective antipsychotic, has low risk for extrapyramidal symptoms, and does not cause elevated levels of prolactin as do the full antagonists at D2 receptors. 

Risperidone (Risperdal). Risperidone is also approved by the FDA for the treatment of acute mania. It acts as an atypical antipsychotic at doses up to 4-6mg/day. Over this dose, and at lower doses in children and the elderly, risperidone acts more like a typical antipsychotic in that extrapyramidal side effects are common. 

As you might anticipate, dopamine receptor-blocking antipsychotics lower the functional dopamine/acetylcholine ratio in the nigrostriatal pathway. As a resnlt, the antipsychotics have the same effect in this pathway as idiopathic PD. This is how antipsychotics produce their so-called extrapyramidal side effects (EPS). EPS can take the form of parkinsonism (e.g., rigidity, tremor) or acnte dystonic reactions. 

As a group, these medications have been known by several names. They have been called major tranquilizers. This is not altogether inaccurate these medications do calm or tranquilize. Physicians still use this name sometimes, especially when they re reluctant to use the word psychotic in a discussion with a new patient or his/her family. These medications have also been called neuroleptic, literally meaning seize the nerve cell, in the original Greek. This term is derived from the potential for the medications to cause extrapyramidal side effects. Finally, and most accurately we contend, these medications are called antipsychotics. 

Typical Antipsychotics. Low doses of high potency typical antipsychotics such as haloperidol or fluphenazine (0.5-2mg given once or twice daily) are generally quite effective for psychotic symptoms after TBI. Unfortunately, as noted earlier, many post-TBl patients are susceptible to the extrapyramidal side effects of these medicines, especially if there was any injury to brain regions such as the basal ganglia. Low potency antipsychotics are not a viable alternative, because their anticholinergic and sedative effects are equally, if not more, problematic for patients who have suffered TBI. We recommend using typical antipsychotics, even for psychotic symptoms, as briefly as possible and in the lowest effective dose, if at all. Fortunately, there are now alternatives. 

In addition to parkinsonism, another extrapyramidal side effect is the so-called acute dystonic reaction in which muscles (usually of the face or neck) go into an acute spasm. A dystonic reaction is painful and unpleasant, usually occurs early in treatment, and sometimes occurs after the very first dose of an antipsychotic. Another extrapyramidal symptom is akathisia, a restless inability to relax and sit still. Akathisia can range from a mild restlessness to extreme agitation. Rarely, patients have been known to attempt suicide during severe episodes of akathisia. It is easy to overlook akathisia, because it can easily be mistaken for a worsening of psychosis or anxiety. 

Akathisia. Akathisia is yet another extrapyramidal side effect. The approach to treatment depends on its severity. For mild restlessness, dose reduction or dividing the daily dose to reduce the peak plasma levels of the medication may be successful. If mild akathisia remains a problem, it may be preferable to add a medication to treat this side effect or preferably switch to another antipsychotic or antidepressant that is less likely to cause akathisia. 

Finally, many of the atypical antipsychotics act, at least in part, by blocking activity at the serotonin-2 receptor. This may lessen the potential for extrapyramidal side effects and contribute to reducing psychotic symptoms. Atypical antipsychotics... 

Largactil is a proprietary preparation of chlorpromazine, an aliphatic antipsychotic with marked sedation and moderate antimuscarinic and extrapyramidal side-effects. Serenace is a proprietary preparation of haloperidol, a butyrophenone antipsychotic with marked extrapyramidal side-effects, moderate sedation but not very likely to cause hypotension. Tegretol is a proprietary preparation of carbamazepine, an anti-epileptic drug indicated in partial and secondary generalised tonic-clonic seizures, primary generalised tonic-clonic seizures, trigeminal neuralgia and in the prophylaxis of bipolar disorder unresponsive to lithium. 

Prochlorperazine is a potent phenothiazine antipsychotic drug that is associated with a high risk of extrapyramidal side-effects, a low degree of sedation and of antimuscarinic side-effects. Chlorpromazine is less likely to induce extrapyramidal side-effects but has increased risks of inducing sedation and antimuscarinic side-effects. Olanzapine is classified as an atypical antipsychotic having characteristically much fewer incidences of extrapyramidal... 

The conventional antipsychotics have little effect on the negative psychotic symptoms such as autism, stupor and emotional withdrawal. The so-called atypical antipsychotics, or second-generation antipsychotics, like the heterocyclic compound risperidone, the benzamide sulpiride and several diben-zepines of which clozapine is the best known, have a broader spectrum which means that they also have an effect on the negative psychotic symptoms. Most share a common attribute of working on serotonin receptors as well as dopamine receptors. They have a low risk of extrapyramidal side effects. 

Extrapyramidal side effects (EPS) associated with SSRI medications used as single agents were reported as early as 1979 (Meltzer et ah, 1979). Since then, several case reports have been published on use of fluoxetine (Elamilton and Opler, 1992), paroxetine (Nicholson, 1992), and sertraline (Opler 1994). The SSRI medications in combination with neuroleptics can cause severe EPS (Tate, 1989 Ketai, 1993) above and beyond what may be associated with increased levels of antipsychotic medications (Goff et ah, 1991), and are perhaps related to pharmacokinetic drug interactions. 

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